Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT04227691 |
| Other study ID # |
SJ-689 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 17, 2020 |
| Est. completion date |
June 1, 2022 |
Study information
| Verified date |
January 2020 |
| Source |
Zealand University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
SUMMARY Objective To assess the efficacy of Nd:YAG laser treatment on eccrine sweat
production in the axillae of persons experiencing excessive axillary hyperhidrosis.
Design Randomised, within-person controlled clinical trial.
Setting One Dermatology Department, at a University hospital in Denmark, from 2018-20.
Participants A total of 10 participants enrolled after signing informed consent from the
patients attending the hyperhidrosis clinic.
Interventions Participants will receive one Nd:YAG laser-treatment of either left or right
axilla. The treated area will be cooled with ice during and after laser treatment. Prior to
treatment, patients can use lidocaine-prilocaine 5% cream at the treatment site on an
optional basis.
Main outcome measures Primary outcome measure will be reduced excessive sweat production
(%points) monitored by an iodine-starch test assessed at 1-month follow-up compared to
baseline. A 30% reduction in sweat production in the Nd:YAG laser-treatment relative to
control, will be considered clinically significant.
Key secondary outcome measures include (1) weighing the sweat by gravimetric testing, (2)
patient assessment of sweat production on a Hyperhidrosis Disease Severity Scale (HDSS) -
also assessed at 1 month from baseline. Safety around the use of Nd:YAG laser-treatment will
be monitored by registering pain during treatment on a visual analogue scale, as well as
monitoring of adverse events immediately as well as one week after treatment. As for the
purpose of further exploratory analyses (both benefits and harms), all outcome measures will
be re-collected 24 months after treatment.
Timelines and dissemination For the collection of the primary data (i.e. primary endpoint
being assessed after 1 month), First Patient First Visit (FPFV) will take place in November
2018 and Last Patient Last Visit (LPLV) will be in March 2019.
The investigators plan to present data internationally at e.g. the European Academy of
Dermatology and Venerology as well as nationally to the Danish Dermatology Society and to the
Hyperhidrosis Patient Association. Results will be published in an internationally recognised
peer reviewed (biomedical) journal.
Trial registration: Danish Research Ethics Committee (approved, protocol number: SJ-689);
ClinicalTrials.gov: NCT pending (2018-11-22).
Description:
INTRODUCTION Primary axillary hyperhidrosis is a condition with excessive secretion of sweat
from the eccrine sweat glands of the armpits that affects between 1 and 5 % of the world's
population. Numbers may be underestimated since this chronical disease debuts during
adolescence and is unmentionable in many cultures and social environments. Hyperhidrosis may
lead to malodour and cause large sweat patches on clothes, thus affecting dressing behaviour,
social activities and job opportunities. As a direct consequence, many patients experience
affected psychological and social behaviour, increased mental stress and low self-esteem.
Several treatment modalities exist that may treat axillary hyperhidrosis. Systemic treatment
with anticholinergic tablets is often reserved to hyperhidrosis that affects the entire body
due to a substantial risk of adverse effects. Possible adverse effects (i.e. related to the
intervention) include dry mouth and other mucous membranes, digestive problems, decreased
ability to empty the bladder, visual disturbances and affected nervous system. Localised
axillary hyperhidrosis is often treated by injections of botulinum toxin. Although this
method is effective in many patients the procedure is painful, expensive and has to be
repeated since the effect only last from four to nine months. Recently, heating of the sweat
glands with microwave technology has shown promising efficacy with minimal adverse effects.
However, this treatment is very expensive and is only available at a few sites in Denmark.
Surgery has also been performed, yet short-term and long-term efficiency is inferior to other
methods. Therefore, there is a need for efficient, safe, affordable and widely available
alternatives to treat axillary hyperhidrosis.
An alternative method that have been proposed, could be heating and destroying sweat glands
by Neodynium Yttrium Aluminium Garnet (Nd:YAG) laser or intensed pulsed light (IPL). These
types of non-invasive light devices are widely available at dermatological clinics in Europe
and is well-known to treat vascular lesions and undesired hair growth. The IPL has a 640 -
800 nm wavelength and the Nd:YAG laser a 1064 nm wavelength that penetrates deeply into the
skin and target the melanin of the hair shaft. By adjusting the pulse length according to the
theory of extended photo-thermolysis, light energy can be delivered through the hair shaft
into surrounding sweat glands. A previous pilot study has demonstrated significant and
lasting reduction of axillary hyperhidrosis in six patients treated with Nd:YAG
laser.Treatments were reported safe and efficient without any side effects. Likewise, two
studies of a comparable but invasive Nd:YAG laser technique reported only temporary mild
adverse effects and significant sweat reduction for up to 43 months after treatment. A single
prospective study without a control group demonstrated increased sweat production following
Nd:YAG laser treatment of excessive hair growth. Targeting hair and sweat glands is however
not directly comparable due to different pulse lengths of the delivered energy.
Dynamic optic coherence tomography (d-OCT) is an imaging technique that utilizes infrared
light to create two-dimensional horizontal or transverse images. Penetration depth is
approximately 0.5 - 2 mm 11. The d-OCT technique allows in situ visualization of dynamic
changes in blood flow and superficial skin structures in vital skin. Thus, the eccrine sweat
glands and the surrounding blood supply can be followed over time without taking invasive
tissue biopsies. Previous studies of histological changes after laser treatment of eccrine
sweat glands have only been able to demonstrate limited structural changes and therefore,
there is a need for improved imaging techniques to visualize laser-tissue-interactions.
Aim & Objectives To assess the efficacy and safety of experimental intervention (either
Nd:YAG laser OR IPL treatment) of an axilla with hyperhidrosis, relative to the contralateral
untreated side, and to visualise laser-tissue interactions by Dynamic Optical Coherence
Tomography.
Primary efficacy objective: to assess the effect of one of the experimental interventions
(either Nd:YAG laser or IPL) treatment on eccrine sweat production by comparing treated and
contralateral untreated axillae in patients eligible for botulinum-toxin therapy due to
axillary hyperhidrosis. Sweat production is to be assessed at baseline and at one-month
follow-up primarily by the iodine-starch test and secondly by gravimetric testing and
questionnaires.
METHODS Patient research partners (PRPs) The study is designed without the assistance of
PRPs. Collaboration between patients and professionals in developing and disseminating
research projects is relatively new and the explorative nature and easily quantifiable
outcomes chosen in this study reduces the need for the use of PRP. Should the study support
the use of the new treatment, larger confirmatory studies will be needed and these will
naturally include softer patient-rerouted outcomes and PRP collaboration.
Trial design and allocation ratio In a prospective within-person randomised trial, patients
will be randomly allocated to receive laser treatment or IPL of one axilla while the other
serve as a control (i.e. Right-Left and Left-Right, respectively). Primary endpoint will be
assessed after 1 month. Treatments are performed with a combined platform of non-ablative 640
- 800 nm IPL and 1064 nm long-pulsed Nd:YAG laser (Lumenis M22 system, Lumenis Ltd.) and
laser energy is applied according to patient skin type.
Settings and locations where the data will be collected This project will take place from
autumn 2019 to spring 2021 in an established research environment in the Dermatologic
Department at Zealand University Hospital Roskilde. All patients will be included from
January 2020 to June 2020 and will if possible be re-evaluated two years later.
Professor, doctor in medical science and Head of Department Gregor Jemec is principal
investigator. Daily leader will be medical doctor, PhD Elisabeth Hjardem Taudorf (EHT).
Medical doctor and PhD-students Mattias Hennig and Linnea Thorlacius will participate in
daily study activities. The department accounts for all study facilities and technical
equipment. The study has been approved by the Danish Research Ethics Committee (protocol
number: SJ-689). Before enrolling the first patient, the trial was registered with
clinicaltrials.gov (NCT Identifier: Pending).
Interventions The intervention under investigation is one treatment with 640 - 800 nm IPL or
non-ablative long-pulsed 1064 nm Nd:YAG laser (Lumenis M22 systems, Lumenis Ltd). Laser or
IPL energy will be applied according to patient skin type. Skin will be cooled during and
after treatment to reduce inconvenience. On an optional basis, patients may also receive
topical anesthesia by lidocaine gel prior to treatment (EMLA 5%, Astra-Zenica, København S,
Danmark). All patients will receive one treatment and will be followed up after one month. If
possible, patients will be contacted in order to perform a long-time follow up after 24
months. After completion of the project, patients are offered laser or IPL treatment of the
axilla, which served as a control in the study.
Power and Sample size considerations A sample size calculation was performed based on the
assumptions that the main outcome measurement (the iodine-starch test for sweat) is
continuous in nature, fairly normally distributed, and that an additional improvement in the
intervention side of 30%points (assumed standard deviation=25% with a correlation of 0.5)
will be considered clinically relevant. For a paired t-test of a normal mean difference with
a two-sided significance level of 0.05 (p< 0.05), a sample size of 8 pairs is required to
obtain a power of at least 80% to detect a mean difference between pairs of 30% (the actual
power is 82.8%). It was decided to include and (within-person) randomise 10 patients for each
intervention in order to consider a potential risk of drop-outs; a sample size of 10 pairs
has a power of 92% to detect the mean difference between pairs of 30%.
As an extra exploratory objective, the investigators will explore whether the use of Nd:Yag
laser or IPL treatment have a different outcome after assessing the overall benefit or "both
of the experimental treatments". Thus, it was decided for pragmatic reasons to include 20
patients in total; 10 of them treated with Nd:Yag laser on the experimental side, whereas the
other 10 will receive IPL treatment on the experimental side.
Randomization Sequence generation, allocation concealment, and implementation This is an
intra-person study, comparing outcomes within participants. All participants will receive
active treatment on one axilla (Active-Right|Control-Left and Control-Right|Active-Left,
respectively). The implied subgroups of which axilla to receive active long-pulsed Nd:YAG
treatment or IPL will also (like right/left) be selected based on a computer generated table
of random numbers using SAS Proc Plan developed by an external biostatistician/author with no
clinical involvement in the trial (RC). The contralateral axilla will serve as control.
The allocation will be concealed in a password-protected computer file only accessible by the
biostatistician. Individual allocations will be held in sealed, opaque, consecutively
numbered digital files, and forwarded individually to the principal investigator sequentially
as an active feedback mechanism after receiving a scanned copy of the informed consent form.
In addition, treatment of left or right axilla with either Nd:YAG or IPL will be directly
communicated from the data manager to the daily leader of the project (EHT) This procedure
will ensure that participants, study staff, and outcomes assessors will remain blinded to
subsequent treatment allocations throughout the trial.
Statistical methods A detailed statistical analysis plan (SAP) will be developed during data
collection. In brief, the analyses will be based on mixed linear models, with a random effect
for participant (1, 2, 3, …, to 20) with a fixed effect for group (active or placebo), axilla
(right or left), and the experimental intervention of secondary interest (Nd:YAG or IPL). For
the primary analyses the type of experimental intervention (Nd:YAG or IPL) will be included
as a main effect only; secondarily if the primary test hypothesis is rejected (p <0.05; H0:
μActive = μPlacebo) the investigators will add a test for interaction to compare the net
benefit for Nd:YAG vs. Placebo and IPL vs. placebo.
PERSPECTIVES Given a successful outcome of an investigation of long-pulsed Nd:Yag laser or
IPL treatment for axillary hyperhidrosis, the laser treatment could potentially be
implemented in the everyday practice, since Nd:YAG lasers and IPL devices are already
widespread in European dermatological hospital departments and clinics.
Data will be presented and published internationally. This new treatment holds the potential
to provide long-lasting sweat reduction in patients suffering from axillary hyperhidrosis.
Patients may benefit from improved self-esteem, prevention of social anxiety, and better job
opportunities, providing a positive personal development for patients, who presently suffer
from a socially unacceptable and neglected chronic disease.
